A fully complementary, high-affinity receptor for phosphate and sulfate based on an acyclic tris(urea) scaffold

Article abstract of DOI:10.1039/c0cc00937g

A fully complementary tris(urea) receptor for phosphate and sulfate anions has been developed by mimicking the scaffold of terpyridine which shows very high affinities and selectivities toward the tetrahedral anions.

Full text of DOI:10.1039/c0cc00937g

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COMMUNICATION
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A fully complementary, high-affinity receptor for phosphate and sulfate
based on an acyclic tris(urea) scaffoldw
Chuandong Jia,ac Biao Wu,*a Shaoguang Li,ac Zaiwen Yang,ac Qilong Zhao,ac
Jianjun Liang,a Qian-Shu Lib and Xiao-Juan Yang*a
Received 14th April 2010, Accepted 26th May 2010
First published as an Advance Article on the web 23rd June 2010
DOI: 10.1039/c0cc00937g
A fully complementary tris(urea) receptor for phosphate and
sulfate anions has been developed by mimicking the scaffold of
terpyridine which shows very high affinities and selectivities
toward the tetrahedral anions.
just like 2,20:60,200-terpyridine (Scheme 1). L was readily
synthesized by the reaction of p-nitro-phenylisocyanate with
1,3-bis(2-aminophenyl)urea which was obtained from reduc-
tion of 1-(2-nitrophenyl)-3-(2-amino-phenyl)urea by hydrazine
hydrate/palladium on carbon (ESIw).9 The two terminals of L
are equipped with nitrophenyl chromophores which can also
make the urea NH protons more acidic.
Anion recognition has become an area of significant impor-
tance.1 In particular, selective binding of phosphate and sulfate
anions has attracted much attention due to their great bio-
logical and environmental relevance. However, the extraction
of these two ions is highly challenging because of their high
solvation energy, large size and tetrahedral shape.2 In recent
years, some artificial hosts with well-defined backbones for
phosphate and sulfate have been developed, such as macrocycles,3
tripodal4 or cleft-like5 species, and metal ion-assisted frameworks6
bearing multiple urea, amine, amide, and indole groups, etc. as
binding sites. Yet the pursuit of simple and efficient anion
receptors remains a major task for researchers in this field.
The concept of anion coordination firstly proposed by Lehn7
in 1978 has been formally accepted nowadays. Very recently,
Bowman-James3a defined anion coordination in views of
coordination geometry and number, as employed by Werner
for transition-metal coordination chemistry. This theory implies
that we can learn from classical metal coordination not only in
understanding the host–guest interactions but also in the design
strategies for promising receptors in anion coordination.
Our previous work in anion coordination has shown that
selective encapsulation of sulfate ion can be achieved by a
tripodal tris(pyridylurea).4a,b In a continuing search for new
anion receptors with high affinities and selectivities, we turned
to the well known 2,20:60,200-terpyridine (tpy)8 ligand which
possesses high chelating effects and well complemented binding
sites for transition metals; can a tris(urea)-functionalized
receptor be designed to bind sulfate or phosphate in a similar
fashion to the complex M(tpy)2]n+? We thus designed a new
anion receptor (L) with three urea groups arranged in a way
To evaluate the rationality of our design, DFT calculations
were carried out at the B3LYP/6-31G(d,p) level on the inter-
action of sulfate with a simplified ligand (L0) in which the
terminal nitrophenyl groups of L were replaced by hydrogen
atoms (see ESI for detailsw). Encouragingly, the model ligand
L0 displays a high conformational complementarity with
2ꢀ
SO4 ion both in the 1 : 1 and 2 : 1 (host/guest) complexes,
and all NH donors are involved in hydrogen bonding with
sulfate, forming six and twelve hydrogen bonds, respectively.
In the two structures, the receptor adopts the same thermally
stable conformation in which two of the three urea subunits of
a receptor occupy two edges of a triangular face of the
tetrahedral anion and the third urea group is twisted away
to bind with one edge of another triangular face. Two recep-
tors thus form a tetrahedral cage which matches perfectly with
the shape of the anion.
We were able to obtain single crystals of the phosphate
complex of the receptor, (Bu4N)3[L2PO4] (1),10 in a DMSO-25%
water solution of L and TBAꢁH2PO4, in which the receptor L
crystallizes with the fully deprotonated phosphate (PO43ꢀ). A
similar phenomenon was also observed in the crystallization of
TBAꢁH2PO4 with a diindolylurea which resulted in the binding
3ꢀ 5a
The structure of 1
of the anion in the form of PO4
.
(Fig. 1a) presented herein agrees well with the 2 : 1 complex
2ꢀ
of SO4
optimized by DFT computations, with Nꢁ ꢁ ꢁO
distances ranging from 2.752 to 2.901 A (2.829 A on average)
and N–Hꢁ ꢁ ꢁO angles from 152.8 to 170.91 (164.11 on average;
Table S1w). This binding mode, where each urea group chelates
an edge of the tetrahedron (Fig. 1b), also represents the theo-
retically optimal saturated coordination mode for tri-urea
a State Key Laboratory for Oxo Synthesis & Selective Oxidation,
Lanzhou Institute of Chemical Physics, Chinese Academy of
Sciences, Lanzhou 730000, China.
E-mail: wubiao@lzb.ac.cn, yangxj@lzb.ac.cn
b School of Chemistry and Environment, South China Normal
University, Guangzhou 510631, China
c Graduate University of Chinese Academy of Sciences,
Beijing 100049, China
w Electronic supplementary information (ESI) available: Synthesis,
X-ray crystallographic details (CIF file), NMR and UV-vis titrations,
DFT computations, and full citation of Gaussian 03 program. CCDC
765572. For ESI and crystallographic data in CIF or other electronic
format see DOI: 10.1039/c0cc00937g
Scheme 1 Design of the anion receptor L by mimicking the scaffold
of 2,20:60,20 0-terpyridine.
ꢂc
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Fig. 1 (a) Crystal structure of the phosphate complex 1 (non-acidic
hydrogen atoms, solvents and counter cations were omitted for
clarity); (b) Representative illustration of the highly complementary
tetrahedral cage formed by two receptors; (c) Crystal structure of
[Fe(tpy)2]2+
.
ligands and tetrahedral anion which has not been enacted by
experiment before.11
As expected, the structure of this complex is very similar to
that of [Fe(tpy)2]2+ (Fig. 1c) except that the conformation of
the receptor is twisted instead of planar as in the latter. This
conformational change of the host is required by the
host–guest complementarity as the shape of the guest changes
Fig. 2 1H NMR spectra of (a) L (5 mM), (b) complex 1, and (c-g) L in
the presence of various equiv. of PO43ꢀ. (a, b) in DMSO-d6-0.5% D2O
(v/v); (c–g) in DMSO-d6-25% D2O (v/v) with 0.5 M Et3N.
from octahedral-coordinate (Fe2+) to tetrahedral (SO42ꢀ).
3ꢀ
The interaction between L and PO4
in solution was
subsequently investigated (Fig. 2). The 1H NMR spectrum
of complex 1 in DMSO-d6-0.5% water showed very strong
downfield shifts of all urea NH groups (Dd 2.45–3.86 ppm)
polyurea receptors in the development of anion-controlled
molecular switches, as those with polypyridines.8
2ꢀ
3ꢀ
Among the examined anions, SO4 induced the second
relative to the free receptor (Fig. 2b), indicating that the PO4
largest downfield shifts of all urea groups (Dd 1.17 to 1.78 ppm,
Fig. S1w). Similar to the case of phosphate, L showed no
binding with the protonated ion, HSO4ꢀ, so reversible binding
and release of sulfate was also achieved by the modulation of
Et3N and HClO4 (Fig. S4w). Other anions resulted in only
slight or no changes ꢀexcept AcOꢀ which induced comparable
changes with H2PO4 (Fig. S1w). Bearing high basicity and a
complementary Y shape with urea, AcOꢀ can be readily
bound by urea-based receptors.13
ion (0.5 equiv. in the complex) forms strong hydrogen bonds
with all binding sites of the receptor. Furthermore, when
PO4 (as Na+ salt) was titrated to a DMSO-d6-25% D2O
3ꢀ
(v/v) solution of L, distinct downfield shifts for the aromatic
H3 (0.76 ppm), H6 (0.22 ppm) and an upfield shift for H8
(0.78 ppm; see Scheme 1 for the numbering of protons) were
induced on adding up to 0.5 equiv. of PO43ꢀ, and no further
changes appeared with more PO43ꢀ, indicating that the 2 : 1
(host–guest) binding mode is persistent even in such a com-
petitive environment (with 25% water). The large upfield shift
of H8 provides further evidences for the 2 : 1 binding mode
which can bring strong shielding effects on this proton.
In addition, one equiv. of various other anions was added
separately to a DMSO-d6-0.5% water solution of L (Fig. S1w).
Interestingly, in the case of H2PO4ꢀ, two sets of signals
appeared corresponding to the slow exchange of complex 1
UV-vis titration experiments were performed in DMSO to
assess the binding affinity and selectivity. Among the various
examined anions (Clꢀ, Brꢀ, Iꢀ, SO42ꢀ, H2PO4ꢀ, ClO4
,
ꢀ
3ꢀ
(between PO4 and L) and fast exchange of the complex (2)
formed between H2PO4ꢀ and L (Fig. S2w). Such a process has
also been reported in the H2PO4ꢀ-binding behavior of amide
functionalized diindolylureas, and can be attributed to a
hydrogen-bonding-activated proton transfer between the free
and bound anions.5b
Notably, the binding affinity with phosphate is largelꢀy
influenced by the protonation state of the anion, as H2PO4
3ꢀ
induced smaller downfield shifts (0.47–0.85 ppm) than PO4
(Fig. S3w), while H3PO4 induced almost no changes. Thus a
reversible binding of phosphate was achieved by adding one
equiv. of Et3N and HClO4 successively to the solution of
ligand L/H2PO4ꢀ (Fig. 3, the influences of Et3N and HClO4 on
the NMR spectra were excluded by control experiments, see
Fig. S3w). This feature resembles the pH-controlled reversible
binding of Fe2+ by tpy,12 and may imply the potential of such
Fig. 3 HClO4/Et3N modulated reversible binding of phosphate by L
(5 mM, H2PO4 added as Bu4N+ salt, H3PO4 as DMSO-d6 solution
ꢀ
diluted from 85% H3PO4). Less than one equiv. of Et3N was added to
ꢀ
ensure that phosphate is bound in the form of H2PO4 only. The
arrow points to the resonance of the acidic proton of Et3N+H.
ꢂc
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AcOꢀ, NO3 added as Bu4N+ salts), only SO42ꢀ, H2PO4
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ꢀ
ꢀ
,
and AcOꢀ induced remarkable bathochromic shifts. The
2ꢀ
association constant with SO4
K/Mꢀ1 = 7.70 by fitting the titration curves to a 1 : 1 binding
was calculated to be log
mode (Fig. S5w) which was also confirmed by the Job plot
ꢀ
(Fig. S6w). The binding constants of H2PO4 and AcOꢀ were
failed to be calculated due to the coexistence of multiple
equilibriums (Fig. S7 and S8w) which were also demonstrated
by NMR titration experiments (Fig. S2 and S9w). In a
3ꢀ
more competitive environment (DMSO-25% water), PO4
(as Na+ salt) induced remarkable bathochromic shifts and
reached a plateau after 0.5 equiv. of the anion was added.
Fitting the titration curves to a 2 : 1 (host–guest) mode, the
binding constants were calculated as log K11/Mꢀ1 = 5.00 and
log K21/Mꢀ2=12.00 (Fig. S10w). Smaller bathochromic shifts
2ꢀ
were induced by SO4 under such conditions (DMSO-25%
water), and the association constant was calculated as
log K/Mꢀ1 = 4.73 by fitting the titration data to a 1 : 1 mode
(Fig. S11w). Other anions resulted in negligible changes of the
absorption spectrum of L. Moreover, competitive experiments
were also carried out and the results showed that the saturated
3ꢀ
2ꢀ
spectra induced by 10 equiv. of PO4 or SO4 were main-
tained even after addition of 100 equiv. of various other anions
(Fig. S12w).
In summary, we report a fully complementary tris(urea)
receptor for phosphate and sulfate anions with very high
affinities and selectivities as demonstrated by theoretical and
experimental results. The scaffold and dynamic anion binding
behavior of the receptor greatly resemble the terpyridine
ligand, providing a typical case of anion coordination.
This work was supported by the National Natural Science
Foundation of China (Grant No. 20872149).
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ꢂc
This journal is The Royal Society of Chemistry 2010
5378 | Chem. Commun., 2010, 46, 5376–5378